The medicine “Glycine tablets for sublingual applying 0.1 g.” is produced on the base of amino-acetic acid contained in all body cells. Amino-acetic acid is a broad-spectrum metabolite. The drug activates inhibitory processes in central nervous system, it has stressprotective and antistress effect and contributes to the increase of mental capacity.
For medicine production (tablets 0.102 g±7.5%) microcapsules of non-agglomerated crystals of amino-acetic acid covered with water-soluble methylcellulose, MC-100 (wherein MC-100 is a water-soluble methylcellulose having a dynamic viscosity in a 1% water solution (by mass) greater than 0.08 Pa·s, having a methoxy group content of 26-33% by mass, having a water solubility at least 98%, having an ash content no greater than 0.3% by mass, and having a water content no greater than 6% by mass), and magnesium stearate are used.
The pharmacopeia (FC 42-3491-98) comprises a range of tests for quality control of the medicine “Glycine tablets for sublingual applying 0.1 g.” with stressprotective, antistress, nootropic and neuroprotective effect for single or longterm administration in the form of a tablet applied sublingually, containing amino-acetic acid (0.100 g.), water-soluble methylcellulose, MC-100 (0.001 g.) and magnesium stearate (0.001 g.) with a mass of 0.102 g.±7.5% and decomposition period varying from 10 to 30 minutes.
There is analysed identity, mass average, decomposition period, foreign substances, microbiologic purity, quantitative content of amino-acetic acid.
It is commonly known that for identity check there is dissolved 0.05 g. of porphyrized tablets in 50 ml of water for 2 minutes. There is added 0.2 ml. of ninhydrin dissolved in acetone to 10 ml. of the obtained solution and heated up to the appearance of blue-purple colouration.
The stain on the medicine chromatogramme obtained in the test of foreign substances must be on one level with the witness standard substance.
Amino-acetic acid quantitation is enhanced by titration.
The medicine “Glycine tablets for sublingual applying 0.1 g.” like other solid dosage forms produced by various enterprises with equal dosage of a medicine (pharmacologically active substance) and equal content and identity of adjunct (auxiliary) components can differ greatly by pharmacological effect (therapeutic effect).
These differences are caused by technology factors: pulverizing, humidification, microcapsulation, thermal drying, compression parameters which together as well as separately can induce polymorphous modification of medicinal substance.
In particular, compression influences greatly particles specific surface and size modification by elastic and plastic deformation, partial destruction of the compressed material and phase contacts mainly.
The essential factor able to increase or decrease activity of active substances and dosage forms is adjunct ingredients. It is determined by the fact that adjuncts have definite physico-chemical characteristics which can be revealed in different ways depending on conditions. On stages of technology process while obtaining solid dosage forms there can be traced physico-chemical interactions between initial components able to change activity of the medicine and add new functions to adjunct components. Such phenomenon changes the concept about indifference of adjuncts and requires some corrections in the approaches to the drugs quality control, comprising not only determination of the medicine content, its decomposition and dissolving period but also analysis of physico-chemical interaction of medical and adjunct substances in aqueous medium and biologic fluid inclusively. Not only the release rate of active substance but also the intensity degree of pharmacological effect depends on interaction of solid dosage form components (Tentsova A. I., Azhrukhin I. S., “The Dosage Form and Therapeutic Efficacy. (Introduction into Bioinformation)”, Moscow, “Medicine”, 1974, pp. 107-122).
Thus, not only the dosage of a medical substance but also qualitative and quantitative content of auxiliary components can be modified uncontrollably. For modification control of quantitative and qualitative composition of auxiliary components and manufacturing technique there must be developed simple and accessible methods of investigation which provide discovering production violations as well as pharmaceutical ones in the process of certification.
The means and methods of quality control of the medicine “Glycine tablets for sublingual applying 0.1 g.” envisaged by the pharmacopeia (FC 42-3491-98) do not make it possible to check if qualitative and quantitative content of adjuncts corresponds to the obtained one, if the drug preparation technique is observed involving the use of microcapsules in the form of a fraction of active component and lubricating component, magnesium stearate. Therefore, it is impossible to guarantee that the medicine produced provides necessary therapeutic effect, since even considerable deviations of composition and technique in preparation of the medicine “Glycine tablets for sublingual applying 0.1 g.” are not discovered by the known control methods envisaged by the pharmacopeia (FC 42-3491-98).